Aberrant microRNA expression has been implicated in the development of human cancers. Here, we investigated the oncogenic significance and function of miR-23b in glioma. We identified that the expression of miR-23b was elevated in both glioma samples and glioma cells, indicated by real-time polymerase chain reaction analyses. Down-regulation of miR-23b triggered growth inhibition, induced apoptosis, and suppressed invasion of glioma in vitro. Luciferase assay and Western blot analysis revealed that VHL is a direct target of miR-23b. Restoring expression of VHL inhibited glioma proliferation and invasion. Mechanistic investigation revealed that miR-23b deletion decreased HIF-1/VEGF expression and suppressed -catenin/Tcf-4 transcription activity by targeting VHL. Furthermore, expression of VHL was inversely correlated with miR-23b in glioma samples and was predictive of patient survival in a retrospective analysis. Therefore, we demonstrated that downregulation of miR-23b suppressed tumor survival through targeting VHL, leading to the inhibition of -catenin/Tcf-4 and HIF-1/VEGF signaling pathways.
基金:
National High Technology Research and Development Program 863National High Technology Research and Development Program of China [2012AA02A508]; China National Natural Scientific FundNational Natural Science Foundation of China [30971136, 81001128, 81071044]; Program for New Century Excellent Talents in UniversityProgram for New Century Excellent Talents in University (NCET) [NCET-07-0615]; Tianjin Science and Technology Committee [09JCZDJC17600]
第一作者机构:[3]Harbin Med Univ, Dept Neurosurg, Affiliated Hosp 2, Harbin, Peoples R China;
通讯作者:
通讯机构:[1]Tianjin Med Univ, Dept Neurosurg, Gen Hosp, Lab Neurooncol,Tianjin Neurol Inst, Tianjin, Peoples R China;[2]Minist Educ & Tianjin Municipal Govt, Key Lab Neurotrauma Variat & Regenerat, Tianjin, Peoples R China;[6]Tianjin Neurol Inst, Lab Neurooncol, 154 Anshan Rd, Tianjin 300052, Peoples R China
推荐引用方式(GB/T 7714):
Chen Lingchao,Han Lei,Zhang Kailiang,et al.VHL regulates the effects of miR-23b on glioma survival and invasion via suppression of HIF-1 alpha/VEGF and beta-catenin/Tcf-4 signaling[J].NEURO-ONCOLOGY.2012,14(8):1026-1036.doi:10.1093/neuonc/nos122.
APA:
Chen, Lingchao,Han, Lei,Zhang, Kailiang,Shi, Zhendong,Zhang, Junxia...&Kang, Chunsheng.(2012).VHL regulates the effects of miR-23b on glioma survival and invasion via suppression of HIF-1 alpha/VEGF and beta-catenin/Tcf-4 signaling.NEURO-ONCOLOGY,14,(8)
MLA:
Chen, Lingchao,et al."VHL regulates the effects of miR-23b on glioma survival and invasion via suppression of HIF-1 alpha/VEGF and beta-catenin/Tcf-4 signaling".NEURO-ONCOLOGY 14..8(2012):1026-1036